Antibacterial and Cytotoxic Actinomycins Y6-Y9 and Zp from Streptomyces sp. Strain Gö-GS12

Wenlong Cai, Xiachang Wang, Sherif I. Elshahawi, Larissa V. Ponomareva, Xiaodong Liu, Matthew R. McErlean, Zheng Cui, Ashley L. Arlinghaus, Jon S. Thorson, Steven G. Van Lanen

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Four new Y-type actinomycin analogues named Y6-Y9 (1-4) were isolated and characterized from the scale-up fermentation of the Streptomyces sp. strain Gö-GS12, as well as actinomycin Zp (5), which was, for the first time, isolated as a natural product. Structures of the new compounds were elucidated by the cumulative analyses of NMR spectroscopy and HRMS. The 4-hydroxythreonine on the β-ring of 1 uniquely undergoes both a rearrangement by a 2-fold acyl shift and an additional ring closure with the amino group of the phenoxazinone chromophore, and the α-rings of 4 and 5 contain a rare 5-methyl proline. Compounds 2-5 showed potent antibacterial activities against Gram-positive bacteria that correlated with cytotoxicity against representative human cell lines. The combination of a β-ring rearrangement and additional ring closure in 1 rendered this actinomycin significantly less potent relative to the nonrearranged comparator actinomycin Y5 and other actinomycins.

Original languageEnglish
Pages (from-to)2731-2739
Number of pages9
JournalJournal of Natural Products
Volume79
Issue number10
DOIs
StatePublished - Oct 28 2016

Bibliographical note

Publisher Copyright:
© 2016 The American Chemical Society and American Society of Pharmacognosy.

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Antibacterial and Cytotoxic Actinomycins Y6-Y9 and Zp from Streptomyces sp. Strain Gö-GS12'. Together they form a unique fingerprint.

Cite this